The goal of this research is to define the organization and relatedness of viral and cellular proteins at the cell surface and to analyze the cellular expression of endogenous retrovirus genes in relation to cell differentiation. Two main studies are in progress: one directed at the structure, organization and topology of cellular and viral proteins in the plasma membrane; and other, the analysis of the relationship between endogenous retroviruses and tumorigenesis of lympho-hematopoetic cells. One objective is to develop probes for the identification and characterization of viral and cellular proteins at the cell surface. Monoclonal antibodies synthesized by myeloma-spleen cell hybrids and reactive with the cell surface molecules of cultured mouse fibroblast cells have been prepared and are being analyzed. Those antibodies that precipitate cell membrane proteins will be used as probes to study the organization and topography of these proteins in relation to previously purified and characterized proteins of cell endogenous oncornaviruses. Studies of mice have shown a possible correlation between expression of endogenous retroviruses and transformation of hematopoetic cells. Definition of the target cells and identification of differentiation-specific cell surface antigens expressed at various steps of cell maturation is being established through development and characterization of monoclonal antibodies reactive with specific types of mouse bone marrow cells. These probes will be used to investigate the process of hematopoetic differentiation and to study virus-target cell interactions in relation to cell transformation and alteration of the physiological events of cell maturation.